Wang Lu-Kai, Wu Tsai-Jung, Hong Ji-Hong, Chen Fang-Hsin, Yu John, Wang Chun-Chieh
Radiation Biology Core Laboratory, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Stem Cells Int. 2020 Sep 29;2020:6312053. doi: 10.1155/2020/6312053. eCollection 2020.
The lung is a radiosensitive organ, which imposes limits on the therapeutic dose in thoracic radiotherapy. Irradiated alveolar epithelial cells promote radiation-related pneumonitis and fibrosis. However, the role of lung stem cells (LSCs) in the development of radiation-induced lung injury is still unclear. In this study, we found that both LSCs and LSC-derived type II alveolar epithelial cells (AECII) can repair radiation-induced DNA double-strand breaks, but the irradiated LSCs underwent growth arrest and cell differentiation faster than the irradiated AECII cells. Moreover, radiation drove LSCs to fibrosis as shown with the elevated levels of markers for epithelial-mesenchymal transition and myofibroblast (-smooth muscle actin (-SMA)) differentiation in and studies. Increased gene expressions of connective tissue growth factor and -SMA were found in both irradiated LSCs and alveolar cells, suggesting that radiation could induce the fibrogenic differentiation of LSCs. Irradiated LSCs showed an increase in the expression of surfactant protein C (SP-C), the AECII cell marker, and -SMA, and irradiated AECII cells expressed SP-C and -SMA. These results indicated that radiation induced LSCs to differentiate into myofibroblasts and AECII cells; then, AECII cells differentiated further into either myofibroblasts or type I alveolar epithelial cells (AECI). In conclusion, our results revealed that LSCs are sensitive to radiation-induced cell damage and may be involved in radiation-induced lung fibrosis.
肺是一个对辐射敏感的器官，这对胸部放疗的治疗剂量施加了限制。受照射的肺泡上皮细胞会引发与辐射相关的肺炎和纤维化。然而，肺干细胞（LSCs）在辐射诱导的肺损伤发展中的作用仍不清楚。在本研究中，我们发现LSCs和LSC来源的II型肺泡上皮细胞（AECII）都能修复辐射诱导的DNA双链断裂，但受照射的LSCs比受照射的AECII细胞更快地经历生长停滞和细胞分化。此外，如 和 研究所示，辐射促使LSCs向纤维化发展，表现为上皮-间质转化和成肌纤维细胞（α-平滑肌肌动蛋白（α-SMA））分化标志物水平升高。在受照射的LSCs和肺泡细胞中均发现结缔组织生长因子和α-SMA的基因表达增加，表明辐射可诱导LSCs的纤维化分化。受照射的LSCs显示出AECII细胞标志物表面活性蛋白C（SP-C）和α-SMA的表达增加，而受照射的AECII细胞表达SP-C和α-SMA。这些结果表明，辐射诱导LSCs分化为成肌纤维细胞和AECII细胞；然后，AECII细胞进一步分化为成肌纤维细胞或I型肺泡上皮细胞（AECI）。总之，我们的结果表明LSCs对辐射诱导的细胞损伤敏感，可能参与辐射诱导的肺纤维化。
